Tolvaptan, chemically 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methyl benzoyl amino) benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine and structurally represented by Formula 1,
is disclosed in U.S. Pat. No. 5,258,510 (Ogawa et al.) and belongs to a class of arginine vasopression receptor 2 antagonist used to treat hyponatremia associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Globally, Tolvaptan is sold by Otsuka Pharmaceutically Co. under the trade name Samsca®.
According to Ogawa et al., Tolvaptan is purified using column chromatography, which necessitates huge volumes of solvents that is commercially and industrially not a viable technique.
A process for preparing Tolvaptan of Formula 1 from starting material 7-chloro-1-[2-methyl-4-(2-methyl benzoyl amino) benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine of Formula 2 using hydrogenating agent is disclosed in U.S. Pat. Nos. 8,273,735 and 8,501,730 (Torisawa et al.), as shown in the scheme below:

The hydrogenating agent used in this process is in an amount of 0.25 to 1 moles and more preferably 0.25 to 0.5 moles per 1 mole of starting material. This process limits the quantity of hydrogenating agent from 0.25 to 1 mole per 1 mole of starting material to minimize the generation of dehalogenated side product, 5-hydroxy-1-[2-methyl-4-(2-methyl benzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine of Formula 3.

Process for the preparation of Tolvaptan was reported in Bioorganic & medicinal chemistry 7 (1999, 1743-1754). According to the journal, Tolvaptan of Formula 1 is prepared from starting material of Formula 2 in 30% yield, as shown in the scheme below:

In this process, the solvent used is methanol and sodium borohydride is used as hydrogenating agent in an amount of 1.5 moles per 1 mole of starting material of Formula 2. The purity of the product is not mentioned in the journal but low yield (30%) makes this process industrially non-viable.
The low yield in chemical process is due to incomplete conversion of reactants into product and/or due to, formation of side products or impurities. Torisawa et al. suggests use of excess amount of sodium borohydride as hydrogenating agent leading to formation of impurities as drawback of the journal's process.
Also, the prior art processes involving use of hydrogenating agent are exothermic in nature suffering from temperature rise, which are not industrially safe. The inventors of the present invention have meticulously devised an industrially safe, feasible and efficient process for the preparation of Tolvaptan (Formula 1) in which conversion of starting material of Formula 2 to Tolvaptan is carried out in alcoholic solvent containing water. Presence of water in reaction mixture helps in controlling temperature rise during the reaction making it industrially safe.